Doctors want to know if rapamycin can prolong fertility

• Rapamycin, an implant and cancer drug, slows cellular growth and reproduction.
• Researchers think it can be used to slow aging, too.
• The first human study of a drug to age the ovaries will soon begin at Columbia University.

Every woman has heard the dreaded phrase: “Your biological clock is ticking.” But at the risk of appearing like an overzealous mother-in-law, it’s true — every month a woman ovulates, some 1,000 potential eggs die inside her. Only one of these follicles becomes viable, resulting in menstruation or pregnancy.

But what if there was a way to slow down the rapid aging process of the ovaries – slow down the ticking of the clock?

A longevity researcher hopes to answer that question, in a first-of-its-kind new aging study to be released at Columbia University this spring.

The study, called VIBRANT (Validating the Benefits of Rapamycin for the Treatment of Reproductive Aging), was designed to measure whether rapamycin can slow aging in the ovaries — but it’s not just about reproductive health. If successful, this first controlled study of the drug rapamycin for aging humans could have widespread implications for helping reduce menopausal pain, and extend the lives of people of all races, using a cheap once-a-week drug that’s already in vogue. Some cancer patients and transplant recipients use it.

The ovaries age quickly – which makes them a great study for antiaging drugs

The basic idea behind the study is that rapamycin can help “preserve the precious finite egg,” explained genetics professor Yusin Suh, director of the Reproductive Aging Program at Columbia. Suh is co-leading this trial with Dr. Ziff Williams, president of the Columbia Fertility Center.

Essentially the goal is to reverse egg freezing — rather than overproducing eggs to store outside the body for later, taking rapamycin will allow women to keep their eggs inside their bodies and keep their ovaries functioning like healthy young men. . If successful, this strategy could herald the entry of a whole new class of medication designed to keep everyone’s bodies healthy and youthful as they age.

“At least, until now,” Suh said, referring to a class of anti-aging drugs that has never been approved for use.

Ovarian aging has all kinds of consequences for women’s health. The onset of menopause coincides with many chronic diseases and health problems, including poor immune function, poor bone density, poor heart health, and metabolic problems. People who go through menopause at a younger age also tend to live slightly shorter lives.

“There is data that shows that menopause actually speeds up aging,” Suh said, arguing that “this tiny little organ controls” much more than fertility or childbearing. It does, really, affect public health. “

The way young, healthy ovaries control the release of eggs is regulated by an enzyme called mTOR, which is the mammalian target of rapamycin. Suh suspects that by slowing this process, with the drug rapamycin, you might be able to safely slow reproductive aging, keeping your ovaries vibrant and young in middle age. This would increase the length of time a woman would be able to bear children, and could lead to regression of menopause. But the doses matter — it blocks mTOR too much, and stops ovulation completely.

Rapamycin actually helps many organisms live longer, healthier lives

Rapamycin, an immunosuppressive drug, has important effects on cellular growth and reproduction that can help slow aging. Already, scientists have shown that rapamycin can extend lifespan and improve the health of flies, mice, and worms.

“It is indisputable that rapamycin extends health and lifespan in all animal models we have tested so far,” Suh ​​said.

The researchers are hopeful that it might have the same effect on elderly dogs, and are testing it on hundreds of them in an ongoing trial. There is also some nascent evidence that rapamycin may improve ovarian function in aged mice.

However, rigorous studies of rapamycin in the elderly are more limited. An experimental drug manufacturer conducted by Novartis in 2014 showed that people over 65 who took rapamycin had a better response to flu vaccines, but it’s unclear what the drug can really do for the health of someone in their 30s or 40s. .

This is why the VIBRANT study will only enroll 50 women ages 38 to 45 in this randomized, placebo-controlled pilot study. To qualify, a woman must be unable to conceive naturally, and is waiting for an egg donor.

“They have normal menstruation, but they have signs of early menopause,” Suh ​​explained.

Suh says the weekly dose of rapamycin the women take is so low that she doesn’t expect to see any of the common side effects of the drug reported by people who have taken it before such as mouth sores or a sluggish cut. healing. But the researchers will closely monitor any adverse reactions, just in case. At the beginning and end of the three-month study period, they will measure a key indicator of reproductive health: the level of AMH each woman has, which corresponds to the number of eggs she has and is a proxy for fertility.

“Help is on the way” to treat infertility

Suh says her connection to this work is very personal, as a mother who experienced many pregnancies when she was younger. For decades, she’d focused only on the “fancy genetics and genomics” of aging, but just as she herself was going through the “very difficult” transition to menopause, she began researching aging ovaries.

“Virtually nothing is known about what happens in the ovaries,” she said. “There is no help. So I would like to say to people like me that help is on the way.”

Worldwide, the World Health Organization estimates that one in six people will experience infertility at some point in their reproductive years. Suh worries that if we don’t discover new solutions to the crisis soon, we won’t be able to support humanity. She also grapples with the inequality inherent in the problem, with women too often forced to consider having children before men, or to forget about it until their hour is up.

“It’s an achievable goal, isn’t it?” She says about delaying reproductive aging. “Conceptually and scientifically, too—we just have to figure out the details.”